Obsessive-compulsive disorder (OCD) affects 1-2% of children and adolescents, causing significant distress and impairments from the unrelenting obsessional thoughts and compulsive behaviors. A unique subgroup of children with OCD has been identified on the basis of the acuity of their symptom onset. The cohort is identified by the acronym PANS, for Pediatric Acute-onset Neuropsychiatric Syndrome. The syndrome is characterized by the foudroyant onset of OCD and/or eating disorder, accompanied by at least two of the following seven comorbidities: 1) Anxiety; 2) Emotional lability and/or depression; 3) Irritability, aggression and/or severely oppositional behaviors; 4) Behavioral (developmental) regression; 5) Deterioration in school performance; 6) Sensory or motor abnormalities; 7) Somatic signs and symptoms, including sleep disturbances, enuresis or urinary frequency and others. For full description, see: Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). Pediatr Therapeut 2012, 2:2 http://dx.doi.org/10.4172/2161-0665.1000113 The clinical description of PANS arose from investigations of a group of children with acute-onset OCD whose symptoms appeared to arise as a consequence of common childhood infections, including Group A streptococcal (GAS) infections (strep throat and Scarlet fever). Children whose symptoms begin or exacerbate following GAS infections may belong to a subgroup of neuropsychiatric disorders identified by the acronym PANDAS (for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The postulated etiology for the PANDAS subgroup is that specific strains of Group A streptococci (GAS), in genetically susceptible individuals, elicit the production of cross-reactive antibodies which recognize antigens not only on the GAS cell wall, but also in the host brain tissue, eliciting obsessions, compulsions, tics and other neuropsychiatric symptoms. The cross-reactive antibodies have been shown to correlate with other anti-streptococcal antibodies and also with neuropsychiatric symptom severity, with highest titers seen in children acutely ill with Sydenham chorea or PANDAS symptomatology. Research at NIH and elsewhere has revealed that: the PANDAS subgroup has a specific and identifiable symptom course (marked most notably by the acute, abrupt, overnight onset of symptoms (zero to sixty in less than 24 hours); the cross-reactive antibodies correlate with both GABHS infection status and neuropsychiatric symptom severity; passive transfer of the cross-reactive antibodies replicated disease symptoms in animal models; prevention of GABHS infections through antibiotic prophylaxis results in prevention of neuropsychiatric symptom exacerbations; and, treatment of acutely ill children with immunomodulatory therapies specifically, intravenous immunoglobulin (IVIG) or plasmapheresis may produce dramatic reductions in symptom severity. This line of research is unusual, in that it reversed the typical bench to bedside progression and took clinical observations and experiences into the laboratory in search of information about etiopathogenic mechanisms. The results proved exciting, as the cross-reactive antibodies identified antigenic targets in the CNS which might provide new targets for therapeutic interventions. Dr. Swedo, Dr. James Leckman and colleagues at the Yale University Child Study Center, and Dr. Madeleine Cunningham of the University of Oklahoma Health Sciences Center were the joint recipients of an NIH Bench to Bedside award which helped fund a multi-site placebo-controlled trial of intravenous immunoglobulin (IVIG) for severely ill children with PANDAS (Protocol 11-M-0058, NCT 01281969) More than 40 children (3-12 yrs old) will be enrolled in the trial and 35 were randomly assigned to receive an infusion of IVIG or placebo. Long-term follow-up of the participants is ongoing, but data are available from baseline, 6 weeks, 3 months and 6 months evaluations. The double-blind and open-label results are being analyzed to evaluate changes in severity of OCD and related symptoms, overall functioning and adverse effects. In addition to providing information about the utility of IVIG treatment for PANDAS, the trial provided biological samples to be analyzed by Dr. Cunningham, Dr. Kyle Williams (MGH-Harvard), Dr. Mady Hornig (Columbia University) and Dr. Carlos Pardo (Johns Hopkins), with the goal of further delineating the pathologic role of the cross-reactive antibodies, as well as potentially developing biomarkers for disease activity and treatment response. More information about the study is available at: http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2011-M-0058.html